5-HT2C receptors exert inhibitory control over dopaminergic and noradrenergic transmission (Neuropharmacology, 1997, 36, 609, J. Psychopharmacol. 2000, 14 (2), 114–138). 5-HT2C antagonists are accordingly considered to be useful in the treatment of numerous pathologies of the central nervous system (CNS). There may be mentioned, without this list being entirely exhaustive, disorders such as anxiety (Br. J. Pharmacol., 1996, 117, 427), depression (Pharmacol. Biochem. Behav., 1988, 29, 819–820), impulsive disorders (Biol. Psych., 1993, 33, 3–14), sexual dysfunctions (J. Pharmacol., 1997, 11, 72), Parkinson's disease (Drug News Perspect., 1999, 12, 477), migraine (Life Sci., 1994, 54, 641–644), cognitive disorders (Neurosci. Biobehav. Rev., 1999, 23, 1111–1125), sleep disorders (Neuropharmacology, 1994, 33, (¾), 467–471), schizophrenia (Neurosci. Lett., 1996, 181, 65) and appetite disorders such as bulimia and anorexia (British J. Pharmacol., 1998, 123, 1707–1715).
The present invention relates to new indoline compounds which differ from the compounds of the Applications WO 9529177 and WO 9748699 not only in the absence of a pyridyloxy substituent on the 3-pyridylaminocarbonyl group of the indoline but also, especially, in the presence of a benzo group fused to the indoline group.
Surprisingly, those structural changes provide the compounds of the invention with pharmacological activities that are clearly superior to those of the compounds of the Applications WO 9529177 and WO 9748699. The compounds of the invention have been found, especially, to be very active by the oral route.
Use of the benzoindoline radical in the compounds of the invention has accordingly made possible a remarkable improvement in the pharmacological properties.